Non-Electric Treatment of Atrial Fibrillation: When Not to Treat?

Non-Electric Treatment of Atrial Fibrillation: When Not to Treat?

R.F.E. P

Atrial fibrillation (AF) is the most common sustained dysrhythmia in clini- cal practice. Atrial fibrillation can be divided into three categories: paroxys- mal, persistent, and permanent. Paroxysmal AF is AF that has occurred and resolves, then recurs. Persistent AF is AF that does not resolve spontaneously, but aggressive attempts to perform cardioversion have not yet been attempt- ed. Permanent AF is AF that has been unresponsive to multiple attempts to cardiovert.

Approximately 30–45% of paroxysmal cases and 20–25% of persistent cases of AF occur in younger patients without demonstrable underlying dis- ease (lone AF) [1]. In the other cases, AF is associated with several cardiopul- monary or systemic disease. Patients present with a range of symptoms:

none, palpitations, systemic embolism or cardiovascular accident, syncope, angina, exercise intolerance, and congestive heart failure.

Haemodynamically unstable patients should undergo immediate car- dioversion; the choice may be also relatively easy for a patient with sympto- matic AF despite adequate ventricular rate control. Such a patient needs a rhythm control strategy to restore and maintain sinus rhythm to alleviate symptoms. One could also argue that every patient with an initial episode of AF should be offered at least one chance to have sinus rhythm restored by electrical cardioversion without long-term anti-arrhythmic drug therapy.

But what about patients who tolerate AF with minimal or no symptoms?

For many years we assumed that rhythm control would be the best treat- ment approach for patients with AF. The presumed benefits of rhythm con- trol are better relief of symptoms and a lower risk of stroke. In contrast, ven- tricular rate control was used more often as a secondary strategy when sinus

Divisione di Cardiologia, IRCCS Fondazione Salvatore Maugeri, Istituto Scientifico di

Tradate (Varese), Italy

rhythm could not be restored and maintained despite the use of multiple anti-arrhythmic drugs and cardioversions. This approach generally involves the use of drugs that block the AV node, such as beta-blockers, calcium antagonists, and digoxin. Concerns about the rate control approach particu- larly involved the perceived risks of allowing AF to continue, e.g. throm- boembolism and stroke, haemorrhagic complications from anticoagulation, atrial myopathy from long-standing atrial fibrillation, and increased mortali- ty.

The dilemma for patients with asymptomatic or minimally symptomatic AF became magnified as data began to emerge about the risks of anti- arrhythmic drugs, particularly for patients with structural heart disease.

These observations led to concern that the potential beneficial effects of restoring and maintaining sinus rhythm may be offset by the adverse effects of the treatment itself.

Several recent randomised studies would appear to support continuing ventricular rate control alone with appropriate anticoagulation for patients who tolerate AF after ventricular rate control is achieved. However, these studies had important limitations, and, as with any study, we must be cau- tious in interpreting the results and keep in mind what type of patients were studied, which treatment options were studied, and to which patients in your practice the results are applicable.

The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), the largest of these studies, directly compared the two strategies, with total mortality as the primary end-point. A total of 4060 patients who were at least 65 years old or who had other risk factors for stroke were ran- domised to a strategy of rhythm control or rate control. The rhythm control group received anti-arrhythmic drugs and cardioversion as necessary to maintain sinus rhythm. Continuous anticoagulation was encouraged but could be stopped if sinus rhythm had apparently been maintained for at least 4 weeks. The rate control group received AV nodal-blocking agents and con- tinuous anticoagulation, with the goal of a heart rate ≤ 80 bpm at rest and ≤ 110 bpm during a 6-min walking test. Catheter ablation of the AV node with pacemaker implantation could be used if ventricular rate control was not achieved with a combination of drugs. After 5 years of follow-up, more patients had died in the rhythm control group (24% vs 21%), but the differ- ence was not statistically significant. More rhythm control patients were hos- pitalised or had adverse drug effects; ischaemic stroke occurred in about 1%

of patients per year in each group, mostly those in whom warfarin had been stopped or whose international normalised ratio was subtherapeutic. Other studies comparing rate control vs rhythm control treatment strategies showed similar results [2–5].

These studies showed that a strategy of rhythm control was not superior

116 R.F.E. Pedretti

to a strategy of ventricular rate control for older patients with AF. There were no significant differences in mortality or quality of life. The incidence of ischaemic stroke was not reduced by attempts to maintain sinus rhythm.

Also, many patients with stroke (about 50% in the AFFIRM trial and 30% in the RACE trial) were in sinus rhythm at the time of the event. Some of the strokes in the rhythm control groups may have been due to subclinical episodes of AF, raising concern about the practice of stopping warfarin after a patient is presumed to be maintaining sinus rhythm on the basis of symp- tom reporting. This, along with the potential side effects of anti-arrhythmic drugs, could have negated the potential advantages of rhythm control.

The patient population in both studies was reasonably representative of patients with AF seen in clinical practice. However, there were two sources of possible inclusion bias:

- Only patients who were able and willing to tolerate AF after ventricular rate control had been achieved were included

- Patients were relatively old, and the conclusions of these studies may therefore not apply to younger patients

- Follow-up was relatively short. The effects of ongoing AF over long peri- ods of time remain unclear, in particular concerning the consequences of the progression of the atrial myopathy in such patients

- Another important limitation of these studies is that they did not assess other, potentially curative treatments.

Therefore, one could argue that these trials compared two suboptimal strategies, and the most appropriate conclusion may be that a rhythm con- trol strategy using anti-arrhythmic drugs is just as bad or worse than a ven- tricular rate control strategy. Interestingly, the AFFIRM trial investigators recently reported that sinus rhythm is associated with a lower risk of death.

For these reasons, we cannot yet conclude that restoring sinus rhythm has been eliminated as a management strategy for many patients with AF.

Further studies are required to determine the best strategy for younger patients and to investigate alternative treatment strategies.

Atrial fibrillation remains a common problem in medicine; its incidence is projected to increase significantly over the next few decades. The optimal treatment strategy has yet to be clarified, especially because of the large vari- ance in presentation and degree of symptoms among different patients.

Effective stroke prevention remains an important consideration. Recent tri-

als suggest that patients with minimal symptoms may be better served with

simple rate control and anticoagulation rather than aggressive attempts to

restore sinus rhythm, particularly as attempts to maintain sinus rhythm are

costly, time-intensive, and ineffective. For patients with problematic symp-

toms, anti-arrhythmic drug therapy is the first line of treatment, but newer,

invasive procedures are being developed and refined. So far, these invasive

117

Non-Electric Treatment of Atrial Fibrillation: When Not to Treat?

therapies have shown efficacy only in limited patient populations. It is hoped that, as medical knowledge of the mechanisms of AF continues to progress and technologies continue to be refined, improved options will become available.

References

1. Lévy S, Maarek M, Coumel P et al (1999) College of French cardiologists.

Characterization of different subsets of atrial fibrillation in general practice in France: the ALFA Study. Circulation 99:3028–3035

2. Wyse DG, Waldo AL, DiMarco JP et al (2002) A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347:1825–1833 3. Hohnloser SH, Kuch KH, Lilienthal J (2000) Rhythm or rate control in atrial fibril-

lation – pharmacological intervention in atrial fibrillation (PIAF): a randomised trial. Lancet 356:1789–1794

4. Van Gelder IC, Hagens VE, Bosker HA et al (2002) A comparison of rate control and rhythm control in patients with persistent atrial fibrillation. N Engl J Med 347:1834–1840

5. Carlsson J, Miketic S, Windeler J et al (2003) Randomized trial of rate-control ver- sus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol 41:1690–1696

118 R.F.E. Pedretti